TRPC channels form the subfamily of channels in human most closely related to drosophila TRP channels. In terms of structure, this family possesses a number of similar characteristics. At the proximal C-terminus of this sub-family is a TRP box motif containing the invariant EWKFAR sequence and between 3 and 4 ankyrin repeats near the N-terminus. These channels are non-selectively permeable to cations, with a selectivity of calcium over sodium variable among the different members. Many of TRPC channel subunits are able to coassemble.1 The predominant TRPC channels in the mammalian brain are the TRPC 1,4 and 5 and they are densely expressed in corticolimbic brain regions, like the hippocampus, prefrontal cortex and lateral septum.23 The TRPC channels 1,4 and 5 functional group is activated the metabotropic glutamate receptor group 1 agonist DHPG.2
In general, TRPC channels can be activated by phospholipase C stimulation, with some members also activated by diacylglycerol. There is one at least one report that TRPC1 is also activated by stretching of the membrane and TRPC5 channels are activated by extracellular reduced thioredoxin. 4
It has long been proposed that TRPC channels underlie the store-operated channels (SOC) observed in many cell types.5 These channels open due to the depletion of intracellular calcium stores. Two other proteins, stromal interaction molecules (STIMs) and the ORAIs, however, have more recently been implicated in this process. STIM1 and TRPC1 can coassemble, complicating the understanding of this phenomenon.1
TRPC6 has been implicated in late onset Alzheimer's disease.6
- Nilius B, Owsianik G, Voets T, Peters JA (2007). "Transient receptor potential cation channels in disease". Physiol. Rev. 87 (1): 165–217. doi:10.1152/physrev.00021.2006. PMID 17237345.
- Fowler MA, Sidiropoulou K, Ozkan ED, Phillips CW, & Cooper DC (2007) Corticolimbic Expression of TRPC4 and TRPC5 Channels in the Rodent Brain. PLoS ONE 2(6): e573. http://dx.doi.org/10.1371/journal.pone.0000573
- Fowler, M, Varnell, A , Dietrich, A., Birnbaumer, L., & Cooper, DC. (2012) Deletion of the trpc1 gene and the effects on locomotor and conditioned place-preference responses to cocaine. Available from Nature Precedings http://dx.doi.org/10.1038/npre.2012.7153.1
- S. Z. Xu, P. Sukumar, F. Zeng et al. (2008). "TRPC channel activation by extracellular thioredoxin". Nature 451 (7174): 69–72. doi:10.1038/nature06414. PMC 2645077. PMID 18172497.
- Boulay G, Brown DM, Qin N, et al. (December 1999). "Modulation of Ca(2+) entry by polypeptides of the inositol 1,4, 5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): evidence for roles of TRP and IP3R in store depletion-activated Ca(2+) entry". Proc. Natl. Acad. Sci. U.S.A. 96 (26): 14955–60. PMC 24754. PMID 10611319.
- Lessard CB, Lussier MP, Cayouette S, Bourque G, Boulay G. (2005). "The overexpression of presenilin2 and Alzheimer's-disease-linked presenilin2 variants influences TRPC6-enhanced Ca2+ entry into HEK293 cells". Cell Signal 17 (4): 437–445. doi:10.1016/j.cellsig.2004.09.005. PMID 15601622.
- TRPC Cation Channels at the US National Library of Medicine Medical Subject Headings (MeSH)
- "Transient Receptor Potential Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- "TRIP Database". a manually curated database of protein-protein interactions for mammalian TRP channels.